circSLC6A6 Sponges miR-497-5p to Promote Endometrial Cancer Progression via the PI4KB/Hedgehog Axis

Abstract

Background. As a new kind of noncoding RNAs, circular RNAs (circRNAs) have been substantiated to be involved in multiple biological processes. Accumulating studies indicate that circular RNAs (circRNAs) regulate the development of cancers by acting as miRNA sponges. However, the role of circRNAs in endometrial cancer (EC) is rarely reported. This study was aimed at investigating the functional roles of circSLC6A6 in EC. Methods. The qRT-PCR assay was performed to detect the circSLC6A6 expression in EC tissues and cell lines. The luciferase reporter assay was performed to explore the connection between circSLC6A6 and miR-497-5p as well as the connection between miR-497-5p and PI4KB. The colony formation assay, EdU assay, wound healing assay, and transwell assay were performed to examine the proliferation, migration, and invasion of EC cells. The in vivo assay was performed to reveal the function of circSLC6A6 in tumorigenesis. Results. We found that circSLC6A6 was highly expressed in both EC tissues and cells. And circSLC6A6 promoted the proliferation, migration, and invasion of EC cells in vitro. In vivo, circSLC6A6 promoted tumor growth. Besides, a mechanistic study demonstrated that circSLC6A6 could regulate tumor-associated signaling PI4KB/hedgehog pathway by sponging miR-497-5p. Conclusion. This study illustrates that circSLC6A6 plays a role in promoting EC progression via the miR-497-5p-mediated PI4KB/hedgehog pathway. Our study may provide a potential novel biomarker for EC diagnosis or treatment.

Long Noncoding RNA LINC00473 Ameliorates Depression-Like Behaviors in Female Mice by Acting as a Molecular Sponge to Regulate miR-497-5p/BDNF Axis

“…In our study, bioinformatics online tools predicted that LINC00473 might bind to miR-497-5p. Previous studies reported that miR-497-5p was a crucial regulator in inhibiting tumorigenesis, and the aberrant expression of miR-497-5p took part in tumor initiation, cancer cell growth, apoptosis, and invasion [29][30][31][32]. More importantly, miR-497 was verified to be increased in the mouse brain after cerebral ischemia, and inhibition of miR-497 could attenuate ischemic cerebral infarction [33].…”

Circulating and Endometrial Tissue microRNA Markers Associated with Endometrial Cancer Diagnosis, Prognosis, and Response to Treatment

“…miR-497-5p participates in EC progression and could regulate the phosphatidylinositol 4-kinase beta (PI4KB)/hedgehog signaling pathway. In EC, miR-497-5p mimics decreased the expression of PI4KB and hedgehog in HEC-1B cells (p < 0.01), while miR-497-5p inhibitors increased PI4KB and hedgehog expression in HEC-1A cells (p < 0.01) [78]. miR-497-5p transcriptional targets have been identified in other tumor types.…”

Circular RNAs in endometrial carcinoma (Review)

“…circRNAs are stable and specifically expressed both intracellularly and in extracellular fluid (27). Although circRNAs are generally expressed at low levels (27), increasing evidence has demonstrated that circRNAs are involved in EC (28)(29)(30). circRNAs carry multiple microRNA (miRNA/miR) binding sites, and regulate the activity of target miRNAs through their competitive binding, thereby inhibiting the transcription of downstream products (31).…”

“…circRNAs are closely involved in the regulation of cell proliferation via multiple pathways. At present, several studies have demonstrated that circRNAs adsorb miRNAs through numerous pathways and fulfill a role in EC development (28,29,71). For example, circIFT80 [circBase ID (http://www.circbase.org/), hsa_circ_0067835], circWHSC1, circSLC6A6, circATP2C1 (circBase ID, hsa_circ_0005797) and circPOLA2 participate in the invasion, proliferation and metastasis of EC through the adsorption of miR-324-5p (71), miR-646 (28), miR-497-5p (29), miR-298 (30) and miR-31 (70), respectively.…”